Bonecchi R, Bianchi G, Bordignon P P, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray P A, Mantovani A, Sinigaglia F
Istituto di Ricerche Farmacologiche "Mario Negri", I-20157 Milan, Italy.
J Exp Med. 1998 Jan 5;187(1):129-34. doi: 10.1084/jem.187.1.129.
T helper cells type 1 (Th1s) that produce interferon-gamma predominantly mediate cellular immune responses and are involved in the development of chronic inflammatory conditions, whereas Th2s which produce large amounts of IL-4 and IL-5 upregulate IgE production and are prominent in the pathogenesis of allergic diseases. The precise factors determining whether Th1- or Th2-mediated immune responses preferentially occur at a peripheral site of antigen exposure are largely unknown. Chemokines, a superfamily of polypeptide mediators, are a key component of the leukocyte recruitment process. Here we report that among four CXC (CXCR1-4) and five CC (CCR1-5) chemokine receptors analyzed, CXCR3 and CCR5 are preferentially expressed in human Th1s. In contrast, Th2s preferentially express CCR4 and, to a lesser extent, CCR3. In agreement with the differential chemokine receptor expression, Th1s and Th2s selectively migrate in response to the corresponding chemokines. The differential expression of chemokine receptors may dictate, to a large extent, the migration and tissue homing of Th1s and Th2s. It may also determine different susceptibility of Th1s and Th2s to human immunodeficiency virus strains using different fusion coreceptors.
主要产生干扰素-γ的1型辅助性T细胞（Th1）主要介导细胞免疫反应，并参与慢性炎症性疾病的发展，而产生大量白细胞介素-4和白细胞介素-5的Th2细胞上调免疫球蛋白E的产生，在过敏性疾病的发病机制中起重要作用。在抗原暴露的外周部位，决定优先发生Th1介导还是Th2介导的免疫反应的确切因素很大程度上尚不清楚。趋化因子是多肽介质的一个超家族，是白细胞募集过程的关键组成部分。我们在此报告，在所分析的4种CXC（CXCR1-4）和5种CC（CCR1-5）趋化因子受体中，CXCR3和CCR5在人Th1细胞中优先表达。相反，Th2细胞优先表达CCR4，在较小程度上表达CCR3。与趋化因子受体的差异表达一致，Th1和Th2细胞分别对相应趋化因子发生选择性迁移。趋化因子受体的差异表达可能在很大程度上决定Th1和Th2细胞的迁移和组织归巢。它也可能决定Th1和Th2细胞对使用不同融合共受体的人类免疫缺陷病毒株的不同易感性。
